he price of CAR-T therapy often dominates the conversation. Yet for patients and families, the true value of these therapies cannot be measured by cost alone.

That question framed a multidisciplinary discussion during the 2026 DIA Global Annual Meeting, where a panel of patient advocates, clinicians, and reimbursement experts explored how CAR-T therapies are challenging long-held assumptions about value, access, and sustainability. Although the conversation centered on oncology, the themes that emerged reach far beyond cancer. They point toward a future in which healthcare systems must evolve as rapidly as the science they are intended to support.

CAR-T: A Stress Test for Modern Healthcare

Few innovations illustrate this challenge more clearly than CAR-T therapy.

Unlike many traditional treatments that are delivered repeatedly over months or years, CAR-T may require a significant upfront investment while offering the potential for durable remission, and, for some patients, years without additional therapy. Yet the reimbursement and health technology assessment (HTA) systems used to evaluate these treatments were largely designed around chronic disease management, recurring treatment cycles, and annual budget planning.

The US experience also illustrates that these systems can adapt. Changes to Medicare payment policy, including the creation of a dedicated payment category for CAR-T, helped address some of the challenges associated with the substantial costs of delivering these therapies. Yet an important question remains: how can reimbursement and assessment approaches capture benefits that may extend well beyond a single payment year or budget cycle?

Rather than creating new problems, CAR-T has exposed existing ones. It has become a real-world stress test for healthcare systems, revealing a growing disconnect between what modern medicine can accomplish and how healthcare systems evaluate, reimburse, and deliver innovation.

Importantly, this challenge is unlikely to remain confined to oncology, the first therapeutic area where a CAR-T cell therapy was approved and commercialized. Cell and gene therapies are rapidly expanding into additional disease areas, raising broader questions about whether today’s policies are prepared for tomorrow’s medicine.

The Therapy Is Changing Too

The challenge is not static. CAR-T itself is evolving.

The panel pointed to advances that could make cell therapies faster, more scalable, and potentially less costly. Innovations in manufacturing are already shortening the time required to produce some therapies, while emerging approaches—including in vivo engineering of T cells and the development of more readily available or potentially “off-the-shelf” approaches—could further change how these therapies are delivered in the future.

At the same time, researchers are working to overcome some of the biological limitations that have made CAR-T more challenging to apply to solid tumors, including the hostile tumor microenvironment that can limit T-cell function.

These developments could fundamentally change the economics, logistics, and delivery of cell therapy. They also underscore the urgency of ensuring that healthcare systems, reimbursement models, and infrastructure evolve alongside the science.

Looking Beyond the Price Tag

Throughout the discussion, panelists repeatedly returned to one central idea: value cannot be defined by upfront cost alone.

For patients, value may mean seeing children grow up, returning to work, or living years free from repeated hospitalizations. For healthcare systems, it may mean avoiding years of chronic treatment, disease progression, and repeated medical interventions. At the societal level, it extends even further: to caregiver burden, workforce participation, and the long-term sustainability of healthcare.

The patient perspective brought this reality into sharp focus. Often, by the time patients receive CAR-T, they have already undergone months (or years) of intensive treatment, with repeated hospitalizations, mounting medical costs, and the uncertainty of not knowing whether the next treatment will work. Focusing exclusively on the price of a single therapy risks overlooking the cumulative clinical, emotional, and financial costs that came before it.

The discussion also broadened the definition of value beyond what happens after a therapy is administered. Value begins with getting the diagnosis right and identifying the most appropriate treatment for each patient. More precise diagnosis and treatment selection could help reduce exposure to ineffective therapies, avoid unnecessary toxicity, and prevent costs associated with treatment pathways that ultimately fail.

One comparison illustrated this shift in thinking particularly well. Vaccination programs, such as those preventing HPV-related cancers, have long been accepted because of the substantial health and economic benefits they generate over time, even though those returns are realized many years after the initial investment. The panelists suggested that transformative therapies may require a similar perspective: one that recognizes lifetime value rather than focusing primarily on immediate expenditure.

Seen through this lens, CAR-T is prompting the healthcare system to ask a much larger question:

Access Is the Next Innovation Challenge

Scientific breakthroughs alone do not improve outcomes if patients cannot benefit from them.

The panel emphasized that access challenges extend well beyond reimbursement. Geographic location, referral pathways, manufacturing capacity, provider expertise, and healthcare infrastructure all influence whether eligible patients receive treatment and when.

For many patients, receiving CAR-T still requires traveling long distances to specialized treatment centers. The discussion highlighted families who had to raise money simply to travel to treatment, as well as patients whose disease progressed while they waited a long time for access. For some, obtaining a visa can become part of the treatment journey. In these situations, the distance between regulatory approval and actual treatment can be measured in weeks, months, or years, or, for some patients, in whether treatment arrives in time for them. Delays in referral or manufacturing can have further profound consequences, particularly for rapidly progressing diseases. But as one panelist put it, for patients, these barriers are rarely experienced as abstract policy problems.

As transformative therapies become more common, success will increasingly depend on strengthening partnerships between specialized centers and community providers, expanding clinical expertise, and ensuring that advanced therapies reach patients wherever they live.

The patient perspective served as an important reminder that these barriers are never simply logistical or financial. They shape treatment decisions, create uncertainty for families, and ultimately determine whether scientific breakthroughs become real-world improvements in care.

Innovation only changes lives when patients can access it.

Precision Medicine Starts Earlier

The discussion also reflected a broader evolution in precision medicine.

Rather than asking which treatment should be used after multiple therapies have failed, the focus is increasingly shifting toward identifying the right intervention earlier in the disease journey. Earlier molecular testing and improved diagnostics can help avoid ineffective therapies, reduce unnecessary toxicity, and connect patients with the most appropriate treatment sooner.

For one panelist, this question was also deeply personal. By the time he received CAR-T, he had already undergone multiple treatment regimens and an autologous stem-cell transplant. His experience raised an important question: could earlier identification of the most appropriate treatment have changed his treatment journey and potentially reduced some of the clinical and financial burden associated with interventions that ultimately did not provide a lasting benefit?

The implications extend beyond any individual treatment journey. More precise diagnosis and treatment selection can help healthcare systems avoid the costs of ineffective interventions while ensuring that patients have an opportunity to receive the therapies most likely to benefit them at the right point in their disease journey.

This evolution represents more than an incremental improvement in cancer care. It signals a broader transition: from reacting to disease toward anticipating it, using biological insights to intervene earlier, more precisely, and with greater potential for long-term benefit.

From Cancer Care to Healthy Aging

Perhaps the most forward-looking portion of the discussion explored what today’s oncology breakthroughs may mean for the future of medicine.

Advances in understanding the biology of aging suggest that many chronic diseases, including cancer, Alzheimer’s disease, cardiovascular disease, and diabetes, share common biological mechanisms. Researchers are increasingly exploring whether therapies that target these underlying pathways could delay or prevent multiple diseases rather than treating each one individually after it develops.

Within this broader context, CAR-T also illustrates how technologies originally developed for cancer may eventually find applications beyond oncology. Early research is exploring whether engineered cellular therapies, including CAR-T approaches directed at senescent cells, could eventually have applications beyond cancer. These approaches remain investigational, but they illustrate how technologies developed for one disease area may ultimately be applied to broader biological mechanisms of disease and aging.

The panel emphasized that the future is not simply about extending lifespan; it’s about extending healthspan: enabling people to remain healthier, more independent, and free from disease for longer.

If healthcare systems struggle today to measure the long-term value of curative cancer therapies, the same challenge will arise as medicine increasingly focuses on preventing disease, slowing biological aging, and improving healthspan. The longer the benefits of an intervention take to materialize, the more difficult they may be to capture within traditional reimbursement and valuation frameworks. This underscores why discussions about transformative therapies increasingly intersect with broader questions of societal investment, and whether healthcare systems are equipped to recognize value that unfolds over decades. Even modest gains in healthy years of life have the potential to generate profound benefits for patients, healthcare systems, and society.

Redefining Value for Tomorrow’s Medicine

The discussion ultimately returned to a simple but profound idea: healthcare systems must evolve as rapidly as the science intended to support them.

The panel’s proposed solutions were as multidimensional as the challenge itself. Bringing transformative therapies closer to patients will require stronger community infrastructure and partnerships beyond specialized centers. Advancing precision medicine can help identify the right treatment for the right patient earlier in the disease journey. At the same time, continued innovation in manufacturing could make cell therapies faster, more scalable, and potentially less costly, while advances in regulatory science could help reduce unnecessary development burdens without compromising patient safety. Public investment in advanced therapies and infrastructure will also be important to sustaining this progress.

Together, these changes point to a broader need for the healthcare ecosystem to evolve in concert. Payment and reimbursement models must also adapt to recognize benefits that may extend well beyond the initial treatment and across a patient’s lifetime.

CAR-T may have been the catalyst for this conversation, but it is unlikely to be the last therapy to challenge existing assumptions.

The future of medicine is increasingly defined by interventions that promise not merely to manage disease but to alter its trajectory—or even prevent it altogether.

As that future comes into sharper focus, the question is no longer whether innovation is advancing quickly enough.

It is whether our definition of value can evolve just as rapidly.

very year, clinical trial sponsors spend an estimated 20% of a study budget on monitoring activities, a significant portion of which exists to reconcile what was documented in a paper binder with what ultimately lives in the electronic data capture (EDC) system. The data was already captured. It was already reviewed and signed by a clinician. Yet the industry has built an entire infrastructure dedicated to transcribing it again, checking it again, and resolving discrepancies that should never have existed in the first place.

Why Has the Conversation Changed?

Site source—the documentation of clinical trial data at the point of care—has been a persistent friction point in drug development for decades. Paper source documents, followed by parallel electronic systems that still required manual transcription into sponsor EDCs, created a workflow that is simultaneously labor-intensive for sites and expensive for sponsors to monitor.

What is different today is the convergence of three forces. First, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have clarified that electronic records generated at the site can serve as the primary source, removing a long-standing ambiguity that made sponsors cautious about accepting anything other than paper. Second, the technology infrastructure, site-side platforms, EDC integration standards, and connectivity between systems have matured enough to make seamless data flow operationally realistic. Third, and perhaps most importantly, sponsors are under more pressure than ever to reduce trial timelines and per-patient costs. The administrative overhead embedded in traditional source-to-database workflows has become a visible target.

A panel of study site operators, CRO leaders, and technology vendors mapped the terrain of this transition, not as a future-state aspiration but as a present-day operational reality with a clear set of remaining barriers, at the DIA 2026 Global Annual Meeting session “Reimagining Site Source.” The crowd, and the questions that kept coming throughout, were a signal in themselves: Industry knows something needs to change, and it is actively looking for the path forward.

What Central eSource Actually Changes

The operational impact of central eSource, where a site uses a single, sponsor-agnostic platform to capture source data that is then mapped directly to the EDC system, is most visible at the site-coordinator level. Under the traditional model, a site coordinator documents an assessment in a paper chart or site-specific electronic record, then re-enters that data into a sponsor-provided EDC. When queries are generated, the coordinator must reconcile two records that should have been one in the first place. This dual-entry workflow, repeated across every data point in every visit across every active study, is where coordinators spend their time and where transcription errors often occur.

Sites that have moved to central eSource report measurable reductions in query rates and in the time required to resolve the queries that do arise. These examples include a 70% reduction in query tracking and a 32% reduction in coordinator time. More importantly, they report that coordinators spend more time with patients and less time with keyboards. For a site running 10 to 20 concurrent studies, the cumulative effect on capacity is significant. The data does not have to be re-entered because it was never separated from the source in the first place.

For sponsors and CROs, the implications are equally direct. Remote monitoring becomes more meaningful when the data available remotely is the same data the site generated rather than a downstream copy that may have already introduced transcription error. Source data verification (SDV) rates, still mandated at 100% in many sponsor protocols despite a decade of risk-based monitoring guidance from, for example, the FDA and EMA, become less justifiable when the source and the EDC are the same record.

What makes this model work in practice, and what became clear in the DIA discussion, is the balance between standardization and site autonomy. Sponsors can equip sites with a protocol-driven template that defines the data required for a given study yet still give sites the ability to add procedures and configurations specific to their workflows. A site coordinator may have established processes that predate any given sponsor relationship. Those processes represent institutional knowledge, refined over years of study execution. A central eSource model that forces sites to abandon institutional knowledge in favor of rigid sponsor templates will fail. However, a model that treats the sponsor template as a foundation rather than a ceiling, and preserves space for site-specific documentation alongside it, creates something more powerful: a record that meets sponsor data requirements while reflecting how care is delivered at that site. The combination of those two layers is where central eSource becomes a durable infrastructure investment instead of just another point-of-problem solution.

The Four-Party Alignment Problem

The gap between what central eSource can deliver and what the industry has adopted reflects a coordination challenge more than a technology challenge. Making site source work at scale requires four parties to change behavior simultaneously: sites, sponsors, CROs, and technology vendors.

Sites have legitimate concerns. Every sponsor-driven technology mandate they have accepted over the past 15 years has added to a stack of point-solutions they are responsible for training on, maintaining, and switching from study to study. The ask embedded in central eSource—adopt a platform that works across your entire study portfolio, not just for one sponsor—is fundamentally different from previous mandates, but sites have no guarantee that sponsors will honor it. The site that invests in an eSource infrastructure still risks being told by a new sponsor that they must use a different system.

Sponsors, for their part, have written EDC and data management requirements into contracts and requests for proposals that assume traditional source-to-EDC transcription. Changing those requirements calls for agreement across clinical operations, data management, and regulatory functions, and often requires renegotiating language with CRO partners as well. The path of least resistance is to leave the language as is.

CROs sit in the operational middle. They are responsible for delivering sponsor mandates across global site networks, and they carry the monitoring cost that central eSource would reduce. They also carry the contractual and change-management risk of asking sponsors to accept a different monitoring model. The financial incentive for CROs to advocate loudly for a model that reduces billable monitoring hours is not straightforward.

Technology vendors have historically built platforms with proprietary data models that make interoperability a commercial negotiation rather than a technical default. Until integration between site-side eSource platforms and EDC systems is treated by the industry as a standard way of conducting research at the site rather than as a billable integration project, the friction lives in the technology layer even when the parties are aligned in principle.

What Each Party Must Do Differently

The path to scale is not complicated in concept, though it is significant in execution. Each party in the four-party model has a concrete role:

• Sites must evaluate central eSource platforms not study by study, but as a portfolio infrastructure investment, selecting a platform that can serve as their system of record across all active studies, regardless of sponsor.
• Sponsors must write protocol and data-management specifications that describe the data they require, not the workflow by which they expect to receive it. Workflow-neutral specifications allow sites to use the technology that works for them while still meeting sponsor data requirements.
• CROs must reframe what monitoring means when source and EDC are unified. Risk-based monitoring, already endorsed by the FDA and EMA, becomes far more operationally tractable when query rates fall and remote data access improves.
• Vendors must treat interoperability as a baseline, not a differentiator. Proprietary integration paths that require bilateral agreements for every sponsor-EDC-eSource combination will not scale. Industry-wide adoption of common data exchange standards, such as Clinical Data Interchange Standards Consortium (CDISC) models, is the prerequisite for the rest of the model to function.

The Patient at the Center

The efficiency arguments for reimagining site source are compelling on their own. But the more durable argument is patient-centered. Every minute a coordinator spends reconciling two records of the same data is a minute not spent with a patient. Every unnecessary site visit driven by SDV requirements adds to the participant burden that already makes clinical trial retention a persistent challenge.

Cleaner data at the source also means faster and more reliable safety signals. When the data that reaches a sponsor’s safety team has been transcribed, reconciled, and queried along the way, delays (and possibly errors) are embedded in the process. The time from safety event occurrence to detection shrinks when the source record and the database record are the same—and in oncology or rare-disease studies where adverse event detection is time-sensitive, that matters.

The decentralized and hybrid trial models accelerated by the COVID-19 pandemic depend on the same foundational shift. A patient who participates in a hybrid study—some visits at a site, some at home through wearables or telehealth—generates source data across multiple touchpoints. A traditional paper-based or site-siloed source model cannot capture that data cleanly. Central eSource, by treating the platform rather than the location as the source of record, creates the foundation that hybrid trial designs require.

The Time to Move Is Now

The industry has had the regulatory clarity, technology, and clinical logic to move on central eSource for several years. What it has lacked is the coordinated will of sponsors, sites, CROs, and vendors acting in aligned self-interest rather than sequential caution.

The sites that have committed to central eSource are not waiting for permission. They are running studies, building institutional knowledge, and developing coordinator workflows that work. The sponsors and CROs that recognize this are beginning to write contract language that accommodates it. The vendors that treat interoperability as a strategic imperative rather than a competitive threat are beginning to build toward it.

“Don’t get hung up on perfection.”

One of the moments from the DIA session that stuck with many in the room came from a panelist who offered a simple reframe. To summarize: Don’t get hung up on perfection. Industry has a tendency to delay adoption until every edge case is resolved, every integration is mapped, and every workflow is validated. The only way to move the bar forward is to start: to take the step, run the study, and build the institutional knowledge that comes from doing. The model does not need to be perfect to be better than what it replaces. And what it replaces has warts of its own, most of them invisible because they have been normalized over decades.

The other thread that ran through the post-session conversations was the burden side of the equation. Sites are stretched. The complexity of clinical trials keeps rising—more endpoints, more data points, more regulatory requirements per protocol—and the coordinator workforce has not scaled to match. Anything that reduces administrative overhead and returns time to the work of recruiting, retaining, and caring for participants is not a luxury. It is a survival mechanism. That is the argument for central eSource that does not require a spreadsheet: sites that can run more studies with the same team, at the same quality, are the sites that stay in business and keep serving patients.

The friction that slows clinical trials today is not a feature of the work. It is an artifact of a data infrastructure designed for a paper world that no longer exists. Reimagining site source is not a disruption of clinical research, it is a return to the principle that data should serve the trial, not the other way around.

ulticancer early detection (MCED) tests aim to identify cancer in people without any signs or symptoms by detecting cancer biomarkers circulating through the bloodstream. Unfortunately, there is no evidence that MCED tests save lives or improve health. Instead, MCED tests may inadvertently cause harm through complications from follow-up procedures (such as biopsies) for false positives and incidental findings. The increased use of health services for follow-up care may also overburden healthcare systems.

MCED test evaluations must address two challenges: 1) determining whether MCED tests save lives without causing excessive harm and 2) accounting for system-wide impacts from additional diagnostic tests and treatment for patients receiving positive MCED test results.

Challenge #1: Determining Whether MCED Tests Save Lives Without Causing Undue Harm

Early Detection Does Not Necessarily Mean Improved Outcomes
Finding cancers early sounds promising: earlier detection could lead to earlier diagnosis and treatment, which would presumably offer a higher chance of survival. This is not always true, however. Unfortunately, diagnosing cancer earlier is not associated with increased survival for many cancers. Slow-growing cancers may not affect patients fast enough for earlier detection to make a difference, especially in the setting of other health conditions. For example, while increased thyroid-cancer screening in South Korea greatly increased the number of diagnoses, the increased screening did not improve thyroid cancer mortality. At the other end of the spectrum, more aggressive cancers may have low survival rates regardless of the stage of the cancer at detection.

Since MCED tests screen for multiple cancers, including those for which early detection with other modalities may be associated with increased survival and those for which it is not, a trial of MCED testing with an endpoint of detecting cancer at an earlier stage cannot evaluate whether MCED testing saves lives. To do so requires evaluating whether MCED tests detect, with a high degree of accuracy, clinically meaningful cancers that can be successfully treated. Without these characteristics, it is unlikely to reduce all-cause mortality (increase survival). Typically, studies of cancer screening analyze cancer-specific mortality because assessing an impact on all-cause mortality requires a very large sample size when studying a single cancer—sometimes millions of participants—and longer follow-up. As MCED tests screen for many cancers, however, the number of participants needed is much lower: one analysis estimated that the National Health Service-Galleri (NHS-Galleri) trial, the largest randomized controlled trial of an MCED test to date, had high enough enrollment to evaluate all-cause mortality.

Furthermore, unlike early detection and cancer-specific mortality, all-cause mortality accounts for deaths or other harms that could result from the follow-up care needed to determine which positive MCED test results are true positives. This follow-up imaging and testing, such as computed tomography (CT) scans and invasive procedures like biopsies, can have adverse effects. The radiation from CT scans, for example, may eventually cause cancers in a portion of scanned individuals, and invasive procedures can lead to complications such as infection and bleeding.

This is especially concerning as it is likely that many positive MCED test results will be false positives, since cancer screening with MCED tests is intended for those with no symptoms, a population with low cancer incidence. While the false-positive rate varies by the specific MCED test model, a systematic review found a median false-positive rate of 2.2%, and the most recent results for the GRAIL Galleri test show a false-positive rate of 0.4%, or 4 false positives for every 1,000 individuals screened. While these percentages by themselves may seem small, if MCED tests are used as intended for population screening, in which millions of asymptomatic individuals are tested, thousands of individuals will receive false-positive results for every million people screened.

Consequently, evaluating whether MCED tests reduce deaths from all causes is critical for establishing whether MCED testing saves lives. If MCED tests reduce all-cause mortality compared to standard care with acceptable risks of harm, then the lives saved by screening outnumber any potential harms from follow-up care.

Existing Evidence Does NOT Show That MCED Tests Save Lives
Unfortunately, no randomized controlled trial—the gold standard of evidence—has evaluated whether MCED tests reduce deaths from all causes or even cancer-specific mortality compared to standard care. The largest randomized controlled trial to date was the NHS-Galleri trial, a collaboration between the UK’s NHS and GRAIL, the manufacturer of the Galleri MCED test. The NHS-Galleri trial studied reduction of stage III and IV cancer diagnoses, and the results were negative: MCED testing with the Galleri test did not reduce late-stage cancer diagnoses. Even if the results had been positive, however, the NHS-Galleri test would not have been able to evaluate whether MCED tests save lives because reduction in late-stage cancer diagnoses is not consistently associated with a reduction in mortality across all cancers.

Challenge #2: Accounting for System-Wide Impacts from Follow-Up Care

Increased use of MCED tests may also overburden healthcare systems, as increased demand for follow-up care from MCED test findings may delay care for other persons and health issues. In one real-world study, patients who received positive MCED tests required an average of four additional lab tests and two imaging tests, and almost half required procedures such as biopsy or endoscopy, before receiving an actual diagnosis. Yet demand for specialist appointments, imaging, endoscopy, and other diagnostic services often already exceeds health system capacity. As a result, cancer diagnostic wait times have been a long-standing concern in the US, the UK, and around the globe, with patients waiting for months to learn whether they have cancer. Time to diagnosis is especially long for suspected cancers that MCED tests are more likely to come back positive for, including hematological and gastrointestinal cancers.

A recent analysis of the NHS-Galleri trial underscores this concern. In the regions of England that participated in the trial, cancer diagnostic delay rates increased immediately following the trial’s start, even as delay rates fell in nonparticipating regions. This suggests that MCED rollout could have system-wide effects on diagnostic wait times, potentially degrading access to care for all patients referred for investigation of suspected cancer. During a trial, this form of spillover could negatively affect outcomes for control group patients, leading MCED to appear more effective in comparison.

Implications for Patients, Insurers, and Regulators

Despite these evidentiary concerns, MCED tests are already available for use outside clinical trials. In the US, hundreds of thousands have been sold commercially even though no MCED test has received US FDA market authorization because a regulatory loophole allows tests from a single laboratory to be marketed. Similarly, MCED tests are available in Canada because the country’s federal regulatory agency (Health Canada) does not regulate laboratory-developed tests. In Asia, the developer of the Shield MCED test partnered with an insurer to offer the test to patients in Hong Kong, Singapore, and the Philippines. MCED tests are also widely promoted, including on social media and in an advertisement during the latest Super Bowl.

Even though the existing evidence, in our opinion, is insufficient to determine whether the potential benefits of MCED tests outweigh the risks, the first MCED test is currently under review by the FDA. If MCED tests receive regulatory authorization by the FDA or other regulatory bodies worldwide based upon the currently available evidence, we believe that the increased access may lead to premature widespread adoption, potentially exposing patients to unnecessary harm and overburdening health systems. Insurers may also face significant strain from the costs of follow-up care from positive tests. This is especially true in the US, where recent legislation has paved the way for Medicare coverage of MCED tests, contingent on FDA authorization.

To address system-wide consequences, evaluations of MCED tests should include not just patient-level outcomes data, but also system-level measures such as appointment availability and average wait times that could be affected by MCED rollout. Insurers and health systems considering adoption of MCED-based population screening should also carefully weigh whether existing capacity can absorb an influx of additional patients requiring investigation of suspected cancer. In some cases, downstream diagnostic services required for follow-up of positive results may need to be expanded in advance of MCED adoption.

Takeaway

Given these concerns, we are of the opinion that MCED tests should not be used for cancer screening at this time. Before MCED tests receive regulatory authorization and insurer coverage, the tests must be shown to improve patient outcomes and save lives without unduly harming patients or overburdening healthcare systems. To do so, more rigorous evaluations of MCED tests with meaningful clinical outcomes for an asymptomatic population, including survival and system-level measures, such as average wait times, are needed.

n September 2025, DIA launched the DIA Obesity Consortium, a public-private partnership focused on improving the efficiency of obesity drug development, assessing quality of weight loss, and evaluating the comorbidities associated with obesity. Several key developments in the global scientific community earlier in 2025 laid the foundation for this important work (see Background and History). This article outlines the key insights from the DIA’s Executive Roundtable on Obesity Drug Development conducted in April 2025. This summary aims to situate the issues covered within the broader regulatory and scientific landscape that subsequently catalyzed the establishment of the DIA Obesity Consortium in September 2025.

Background and History

In January 2025, The Lancet Commission on Diagnostic Criteria of Clinical Obesity redefined clinical obesity as a chronic, systemic disease characterized by alterations in tissue or organ function due to excess adiposity, distinct from preclinical obesity, where the excess body fat (adiposity) has not yet altered the function of tissues, organs, and overall systems. For diagnosis, the Commission recommended moving beyond Body Mass Index (BMI) alone (which should only be used as a surrogate measure for health risk) and towards confirming excess adiposity with methods like direct body fat measurement or anthropometric criteria such as waist circumference (WC), waist-to-height ratio (WHtR), or waist-to-hip ratio (WHR). These measures, together with clinical manifestations of obesity such as reduced organ or tissue function or substantial, age-adjusted limitations of daily activities, can be used to diagnosis obesity.

In January 2025, FDA issued its draft guidance Obesity and Overweight: Developing Drugs and Biological Products for Weight Reduction for Industry. In this revision, FDA explicitly recognized obesity as a chronic disease characterized by excess adiposity and noted BMI as a measurement that is a standardized, reproducible, and practical endpoint because of its simplicity and strong correlation with total body fat and historical use in clinical and research settings. FDA urged sponsors to engage regulators early when considering proposing alternative measures for enrollment criteria. Further, the guidance emphasized FDA’s continued reliance on body weight as a clinical endpoint in clinical trials of obesity medications (OMs).

As innovation in the treatment of obesity continued to accelerate globally, the 2025 expanding OM pipeline comprised over 150 clinical-stage assets (including multiple assets in phase 3), spanning more than 60 mechanisms of action, with 43% of all anti-obesity medications (AOM) assets being oral therapies. To meet the needs of patients living with obesity, developers are seeking differentiation through multiple dimensions (including efficacy, tolerability, quality of weight loss, convenience, and durability) as this crowded field matures. For example, the distinction between fat and lean mass loss is of high interest, as this could have an impact on patient outcomes.

Very recently (in 2026), new Standards of Care in the field were released: 1) the 2026 ADA Standards of Care in Obesity and 2) the 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome, which support the use of BMI and additional anthropometric measurements (e.g., WHtR and WC) to diagnose obesity. Not only do these recommendations have potentially significant implications for future treatment guidelines, but they will likely impact obesity management payer coverage decisions as well. In 2024, BMI thresholds were removed from the indication statements in the US Prescribing Information for Wegovy and Saxenda (Novo Nordisk), as well as for Zepbound (Eli Lilly), but the reference to patients with obesity as well as those who are overweight and have comorbidities was retained. This is because modern labels for GLP-1 receptor agonists now focus on the specific clinical benefits for the patient, such as lowered cardiovascular risk.

Standardizing Efficacy Endpoints for Quality of Weight Loss

The authors of this article (hereafter referred to as “the authors”) agreed that traditional weight-reduction metrics (total body weight and BMI) do not fully capture changes in body composition (lean muscle mass versus fat mass), nor do they consider the impact on physical function and overall health, which are clinically important benefits of obesity treatments. The limitations of BMI are extensively documented in scientific literature, including by The Lancet, and to some extent, in the most recent FDA guidance. There was, therefore, broad interest from both industry and academic representatives in assessing ways to measure the quality of weight reduction and body composition both during clinical trials and in clinical practice, with a particular focus on preserving lean muscle mass and establishing standardized methodologies to assess that element, the ultimate goal being to determine whether the quality of weight reduction is a more clinically meaningful endpoint than total weight loss alone. Several clinicians noted that the loss of lean muscle mass might be concerning or harmful especially for older people (a conclusion that underscores why it is necessary to characterize and protect vulnerable subgroups from such effects). The authors agreed that the central challenge lies in establishing a clear threshold at which lean mass loss becomes clinically concerning and what body composition treatment goals should look like. As patients with obesity are heterogenous, we need to consider stratifying patients for participation in clinical trials based on their physical functioning.

Additionally, the authors agreed that direct measurement of physical function at baseline would be more reliable than patient self-reported physical function, especially for the purposes of stratification. Several clinicians recommended focusing on functional measurements as key secondary endpoints for phase 3 clinical trials, especially in patients at risk of sarcopenic obesity. Exploring validated digital health tools for remote monitoring of physical activity and function might address potential barriers.

Roundtable participants also discussed how to incorporate qualitative data through exit interviews to understand patients’ perceptions of changes beyond weight loss, and acknowledged the logistical challenges sites encounter when utilizing resources such as MRI for body composition assessments during staffing shortages. Limited access to MRI machines within a reasonable distance of a patient’s residence can also be a problem in routine clinical practice. According to the FDA 2025 guidance, FDA presently regards lean mass loss as a safety endpoint rather than an efficacy endpoint. Based on the roundtable discussion, it is not appropriate at this time to consider a change in body composition alone (e.g., reduction of fat mass, while preserving lean muscle mass during treatment with an OM) as a potential claim for the management of obesity because there is currently no data to establish whether loss of muscle mass relates to a disease state or a manifestation of a disease, and its relevance as a clinical endpoint is not yet well understood. Additionally, changes in structure or function typically need to be linked to a disease state. Therefore, it is currently challenging to directly label benefits related to quality of weight loss or improved physical function in the absence of a link to a specific disease indication, such as sarcopenic obesity.

The authors agreed that the regulatory pathway for claims related to body composition, lean mass preservation, or muscle function, as well as endpoints required to measure these claims, are not clear at present. In response, participants from FDA confirmed that they were open to discussions on this topic with sponsors, clinical trial participants, and other stakeholders from the patient advocacy community. Data-generation efforts studying the impact of changes in body composition are also essential for advancing obesity research, particularly in gaining more insight into the goals of treating obesity and in refining diagnostic criteria.

The authors agreed that we should continue exploring how to include functional outcomes, such as mobility and muscle strength, in the list of endpoints collected during phase 3 obesity clinical trials because they are meaningful to patients. Furthermore, fit-for-purpose Clinical Outcome Assessments that reflect real-life impact on those with obesity are important for healthcare providers as well. Current tools such as the six-minute walk test and the sit-to-stand test show promise but also have limitations, especially when applied across different BMI patient subgroups. It is important to ensure that clinical trial endpoints are not only meaningful and measurable but are also feasible to implement in routine clinical practice so that the outcomes studied can realistically translate into everyday patient care. The authors also agreed that a measurement may still be an important element to capture, even if it is not subsequently included in the label. Currently, waist circumference is still considered an important measurement, yet it has been removed from the new regulatory guidance due to concerns around high operator variability for the measurement, potentially making it unreliable as a primary endpoint in pivotal clinical trials. For the currently approved OMs, weight loss was used as the primary endpoint, even though its direct correlation to meaningful clinical outcomes (morbidity, mortality, quality of life) can be complex and indirect.

Taking this into account, the authors think that FDA is likely to continue to rely on standard weight loss as a primary endpoint unless a clear link between more complex adiposity measures and disease modification is established. Roundtable participants agreed it would be great to see progress in the field but that this would require science-based evidence for evaluation. The authors encourage industry to conduct and publish research that can advance knowledge in this area and encourage further industry collaborations to qualify or validate one or more endpoints in the future through pooling data from their completed clinical trials. Roundtable participants agreed that it is critical for all stakeholders to align the measurements collected from future phase 3 clinical trials to allow data from various ongoing research to eventually be pooled for group analysis and biomarker validation.

Approaches to Comparator Trial Design, Pharmacovigilance, and Safety

The well-publicized effectiveness of new OMs makes it difficult to enroll and retain patients on placebo for extended periods, especially the mandated one year at the maintenance dose. In addition to potential ethical considerations, these factors are beginning to create significant operational challenges for trial enrollment and conduct. Industry representatives shared that it is no longer practical to enroll 1500 placebo patients for phase 3 trials, a significant concern because of the difficulty of retaining placebo patients in these trials given the widespread availability of OMs today. Several companies shared that this factor also impacts discontinuation rates, and that we need to continuously evaluate the ethical implications of long placebo durations when highly effective treatments are available. Attendees from industry were interested in exploring the possibility of alternative approaches that require a smaller number of patients in placebo arms; this could be achieved by using approaches such as incorporating active controls when exploring the design of future obesity clinical trials.

Participating Principal Investigators at US clinical sites advised that fixed-dose regimens are not ideal due to heterogeneity in patient response and tolerability, so flexible dosing would be ideal to offer to patients who are able and willing to participate in clinical trials. It was also suggested that sponsors offer active treatment post-trial completion as an incentive for recruitment. Roundtable participants argued that strong site-patient relationships and early screening for patient commitment are crucial to reduce dropouts once the clinical trial begins.

According to the FDA 2025 guidance, the sample size in obesity trials is driven by safety, not efficacy. Participants discussed that, for obesity drugs with a long development history such as injectable peptide GLP-1s, there might be some regulatory flexibility in determining the sample size, including placebo. Safety databases for various indications could be shared to potentially decrease the number of placebo patients needed. If active control is utilized, it will be challenging to interpret the safety data. The key is to have a control group that can allow an evaluation of the safety of the drug. The authors understand that it is not yet acceptable to the Agency to remove the need for placebo control at this time. Past and current trials could inform future trial designs, and lead to eventual changes in placebo requirements. The 5% change in weight loss included in the recent FDA guidance revision is based on earlier FDA Advisory Committee input and is linked to known cardiovascular benefits associated with that amount of weight loss. In addition, it is scientifically interesting to explore and understand what any additional weight loss means for the patient in terms of CV benefit. Real-world flexible dosing presents challenges for trial analysis and approval.

The concept of a fixed “maintenance dose” (as described in the draft FDA guidance) also becomes complicated when considering long-term management. Industry representatives shared that there is a growing interest among many sponsors in obtaining a “weight maintenance” indication. However, there is still ambiguity around what constitutes a maintenance dose versus a target dose, creating confusion in trial design and clinical guidance, and whether a weight maintenance indication is linked to clinical benefit. Patient goals can also evolve as they lose weight. They may initially aim for a specific weight goal but then desire further weight reduction later as they achieve their target weight. This is highly individualized for each patient. A treat-to-target concept could also be considered. Maintenance may be better evaluated as extensions to clinical trials, instead of new trials. If maintenance is hard to define, “Time to Treatment failure” as a potential endpoint could be considered.

The authors also suggest reconsidering the term “maintenance.” Because obesity is a chronic disease, “treatment for sustainable weight loss” or “target dose” might be more accurate terms since they are less suggestive of a fixed endpoint. Of note, the “maintenance dose” in a clinical trial is not the same as the “clinical weight maintenance state,” which refers to a sustained weight-reduced state. Even though FDA may not oppose a weight-maintenance indication, the authors discussed that it could be very challenging to obtain for an unapproved drug; however, it might be feasible to pursue that approach for an already approved drug. The key will be to consider how the pivotal trials are designed. Regulatory questions about safety data may arise when patients switch to different drugs or take different doses of the same drug after the initial weight-loss goal has been achieved. For example, switching to a drug with potentially less cardiovascular benefit after initial weight loss with a drug that has a better cardiovascular benefit raises safety concerns that would need careful study in a comparative efficacy trial. Randomized withdrawal design studies can be considered for maintenance. Randomizing patients in the treatment arm after study completion to either standard of care or active treatment for a specific time duration could also be considered. The authors agreed that, as long as the options are there, physicians can find a strategy to meet their patients’ needs.

Master Protocols and Clinical Trial Design

Master protocols offer promise but are complex to operationalize in large heterogeneous populations. Key considerations in this case include ensuring that the selected design ensures efficiency without compromising scientific rigor or data integrity. Also, it is desirable to find overlap in disease duration and onset (e.g., obesity and CKD/HF/MASH) with endpoint timing that aligns across comorbidity subgroups. Finally, the group agreed that it is critical to utilize pre-specified endpoints and preserve blinding across groups.

Based on established precedents, the roundtable participants discussed the potential usefulness of basket and umbrella trial designs for OMs. However, broad inclusion of associated diseases without clear mechanistic links or proof of benefit may present significant challenges for regulators. For example, it is well established that comorbidities such as hypertension are strongly associated with obesity. But sponsors may need to justify the mechanism by which the investigational drug impacts that specific comorbidity in the presence of other comorbid conditions. Although more than 200 comorbidities are associated with obesity, certain conditions—particularly cardiometabolic comorbidities—are likely more plausible and clinically relevant targets for further exploration. Therefore, it is the authors’ opinion that FDA may be open to considering new comorbid conditions if a mechanistic link can be reasonably established. The authors also believe that, even though time to first event is a well-established endpoint, FDA might consider accepting recurring events as a primary endpoint as well. The challenge for the latter is that some patients may have many recurring events which impact the results for the entire study arm. In the analysis of composite endpoints for outcome trials, it appears that FDA currently reviews each individual component of the composite endpoint to evaluate their contribution to the overall treatment effect.

Surrogate endpoints are critical for reducing trial duration but must meet certain evidentiary standards. Validated surrogates are used for traditional approval and surrogates that are “reasonably likely” to predict clinical benefit are used to support accelerated approval, followed by full approval with data from confirmatory trials. Two examples were shared at the roundtable where the FDA accepted Letters of Intent to qualify biomarkers in conditions related to obesity drug development:

• Noninvasive tests (vibration-controlled transient elastography [VCTE], e.g., FibroScan) for metabolic dysfunction-associated steatohepatitis [MASH]: diagnostic biomarker to enrich and to identify patients likely to have histopathologic findings of nonalcoholic steatohepatitis (NASH): DDT-BMQ-000084.
• Noncalcified plaque in cardiovascular outcomes. Coronary artery noncalcified plaque volume (NCPV) for detection and quantification of atherosclerotic coronary artery disease: DDT-BMQ-000161.

The authors recommend that the obesity stakeholder community take a sequential approach to validating biomarkers, given that establishing biomarkers as a surrogate endpoint can be a high evidentiary bar. First, an endpoint can be used as a diagnostic or prognostic biomarker in clinical trials while data is being accumulated. Once enough data has been collected to confirm that the proposed surrogate is reasonably likely to demonstrate clinical benefit, then it can be applied as an endpoint in a clinical trial. In this case, it would be important to specify the applicable context of use.

The authors agreed that industry should continue to invest in developing and validating novel surrogate endpoints, especially those linked to real-world functional outcomes. The authors acknowledged the benefit of composite endpoints or coprimary endpoints since they can capture nuanced benefits and evaluate patient-centered outcomes like improvements in mobility, sleep, and daily function.

Next Steps

The power of collaboration between industry, academia, and regulators, together with patients and patient advocacy organizations, will be more important than ever in the obesity drug development arena. Among the key recommendations from the DIA Executive Roundtable was the proposal that DIA take the lead to form a public-private partnership consortium with industry, academia, regulators, other nonprofit organizations, clinicians, and patients in the obesity space to assess comorbidities more efficiently and develop an evidence-generation strategy on endpoints to measure quality of weight loss, including measures of body composition and measures of physical functions. Additional recommendations emphasized that trial design must balance multiple factors such as flexibility, patient retention, and regulatory rigor.

The DIA Obesity Consortium is working diligently to discuss the best strategy for improving the efficiency of future phase 3 clinical trials for OM development. Ensuring that similar endpoints are collected across clinical trials could allow future meta-analysis across companies and bring about biomarker validation, faster regulatory approvals, and eventually global harmonization of requirements across various regulatory agencies. DIA also organized a meeting with European Regulators and stakeholders in Rotterdam on March 23, 2026, before the start of the 2026 DIA Europe Annual Meeting. Furthermore, the results and recommendations of the consortium work were also presented during the 2026 DIA China Annual Meeting in Shanghai and 2026 DIA Global Annual Meeting in Philadelphia, PA (US).

Acknowledgements:

DIA thanks the following FDA experts and leaders for their participation in the April 2025 Executive Roundtable on Obesity Drug Development: Charu Gandotra, Mark Reitman, Yun Wang, Aliza Thompson, Jeffrey Siegel, and Yoonhee Kim.

n the early 1990s, sponsors stopped buying clinical research one study at a time. Faced with growing pipelines, fragmented suppliers, and rising trial complexity, they reorganized how they engaged contract research organizations (CRO). They moved from transactional, study-by-study contracting to preferred-provider relationships, strategic partnerships, and later to functional service provider (FSP) models that allocated entire categories of work to a small number of trusted partners. The shift was uneven, but the direction was clear: Sponsors wanted fewer relationships, deeper integration, and a way to buy reliability and predictability rather than capacity.

This shift raises an objection I have heard in almost every sponsor conversation. Concentrating sites with one provider, the argument goes, puts too many eggs in one basket. This Commentary argues that this objection has it backwards: Allocating volume to a single accountable network does not concentrate risk but in fact reduces it, and it does so in ways that align with where regulators are already pushing the industry.

The Real Risk: Variability, Not Concentration

The concentration-risk argument assumes that every site is equally reliable and that the only variable worth managing is how many baskets you spread your eggs across. Anyone who has run trials at scale knows this is not how sites perform. In my CRO years, we had a saying: Some sites will carry a study, and some will barely move it; the frustrating part was never knowing in advance which was which. Independent research points the same way: roughly half of all sites in a typical global phase 3 trial either fail to enroll a single patient or fall short of their target, a pattern that, according to Tufts Center for the Study of Drug Development research, has held for more than two decades. This uncertainty, not the number of sites, is what undermines trials. It shows up as slow starters, nonenrolling sites, and a long tail of underperformers that quietly drag a study past its timelines.

Variability in site performance is the risk that sponsors should manage. Network-level allocation addresses it directly. An MCRC does not promise that every site performs identically but provides a structure that narrows the spread between the best and worst sites. It does this by applying the same standard operating procedures, the same training, the same technology, and the same governance across all of them. The value of a network is not that any single site is guaranteed to excel. This approach reduces the uncertainty introduced by multiple sources of variability.

The Evidence: What Benchmarking Data Shows

This is more than just my experience talking. The Association for Multisite Research Corporations (AMRC) has benchmarked MCRC performance against other site types in partnership with one of the world’s largest pharmaceutical companies. The analysis covered 40 studies across 100 MCRC sites and 736 non-MCRC sites in the US, all completed since 2020. Some of the findings, on quality specifically, have already been discussed in Global Forum. I want to draw out what they mean for how sponsors buy delivery.

Start with speed, because it is the most visible. MCRC sites moved from final protocol to site ready in an average of 199 days, against 264 days for non-MCRC sites. From site ready to first subject in, MCRC sites took 57 days against 87. That is a meaningful head start on any timeline.

But speed is not the finding that matters most for this argument: Predictability is.

The site-ready-to-first-subject-in cycle was not only faster at MCRC sites, it was more predictable, with a smaller spread around the average. Across the other cycle-time measures, where average performance was broadly similar between site types, MCRC sites were still consistently the more predictable of the two. This is the variability thesis showing up in the data. A sponsor allocating volume to an MCRC is buying a narrower range of outcomes, which is exactly what makes a program plannable and more predictable.

Predictability did not come at the expense of quality. Important deviations as a share of total deviations were lower at MCRC sites, at 13.3% against 14.7%. Query volumes and resolution times were comparable between the two groups, and data-entry timeliness was similar, with MCRC sites again showing less variation. MCRC sites were as productive as their counterparts on enrollment and, critically, had a lower proportion of nonenrolling sites. The long tail of dead-weight sites, which quietly wrecks a recruitment plan, was shorter.

From Part-time to a Professional Undertaking

There is a structural reason MCRC performance is less variable. For most of its history, the site industry grew up as an amateur undertaking. Trials were run by part-time physician-investigators, fitting research around a clinical practice and supported by staff who often moved within a year or two. The result was the well-documented “one-and-done” problem, where a large share of investigators ran a single trial and never returned. Every one-and-done PI is a site that starts from zero, with no accumulated operational learning. Variability is the natural consequence of an industry built this way.

MCRCs change the underlying economics. Research is the core business, not a sideline, so the people running trials stay. AMRC’s benchmarking bears this out starkly. Principal investigator turnover at MCRC sites ran far below that of the wider industry, at 7.8% versus 54.2%, and coordinator turnover was also markedly lower, at 15.4% versus 33%. Stable career research teams are the mechanism that produces low variance. They carry operational memory from one study to the next, and that accumulated competence is precisely what a sponsor is buying when it allocates to a network.

The Diagnosis is Settled

Put the pieces together and the concentration-risk objection collapses. Allocating volume to a single accountable network does not pile up risk; it compresses the variability that causes trials to miss their timelines, and it does so without trading away quality. The data supports the diagnosis. The harder question is what sponsors and MCRCs should each do about it.

Part two of this commentary will set out the practical model: why this shift aligns with where regulators are taking risk-based quality management, what the emerging enrollment data—including a diversified, blinded portfolio of real-world case studies spanning six therapeutic areas—tells us about the power of scale, and the specific commitments that both sides must make for network-level allocation to work. The lesson from the CRO market is that these partnerships succeed only when the metrics, governance, and accountability are built in from day one.

he Association of Southeast Asian Nations (ASEAN) Joint Assessment (AJA) is a voluntary, collaborative procedure that allows pharmaceutical companies to simultaneously submit a marketing authorization application for assessment to and by a minimum of three participating ASEAN National Regulatory Authorities (NRAs). The ASEAN JA framework was established in 2017 under the auspices of the Joint Assessment Coordinating Group (JACG) of the ASEAN Pharmaceutical Product Working Group, with technical advice from the World Health Organization (WHO). Several NRAs have included AJA as one of the formal registration procedures in their guidelines. Since its inception, several products across industries have been approved via the AJA pathway.

Pilot Architecture: The Coordination Model

The pilot employed a centralized coordination model designed to minimize duplication and maximize scientific alignment. Malaysia’s National Pharmaceutical Regulatory Agency (NPRA) served as the Lead NRA, spearheading the joint scientific review (see Table 1 for all participating agencies). This regional effort was bolstered by strategic advisory support from Australia’s Therapeutic Goods Administration (TGA), which provided technical guidance to participating NRAs in a role facilitated by the WHO to provide mentorship.

The methodology relied on a sequential submission strategy to maintain a manageable workflow. The PAC dossier was submitted to and assessed first by all participating NRAs, followed by the LE application. Communication with NRAs was centralized through the Joint Assessment Information Management System (JAIMS), a platform used by the sponsor’s single coordinating affiliate to manage submissions and query responses. The workflow spanned from October 2024 through February 2026, a duration that the sponsor considered reasonable, and transitioned from a collaborative assessment into a national phase where each NRA issued final approvals.

Measuring Success: Timelines and Efficiency

The AJA framework performance was evaluated against Key Performance Indicators focused on review speed and scientific alignment:

• Total approval timelines, including the national phase.
• Number of consolidated AJA questions versus national queries.
• The extent of requirement waivers and cross-border alignment.
• Overall operational gains via centralized coordination.

Table 1 also outlines that PAC approvals were finalized between May and August 2025, and LE between March and April 2026. While the AJA significantly improved timelines in most countries (Figures 2-3), Indonesia’s PAC approval still required 2.8 months (versus the standard 2.0 months) via the AJA pathway (Figure 2). This delay highlights a regulatory disconnect in Indonesia’s “Dual-Review Scenario.” The absence of a formal AJA procedure in Indonesia resulted in parallel processing, which ultimately negates the efficiencies typically gained through collaborative procedures. Significant improvements were also observed in Malaysia, where PAC approval timelines were reduced from 11.8 months via the national procedure to 4.7 months (60%) under the AJA. This momentum carried through to LE, where overall timelines also decreased under the AJA pathway in all participating NRAs. For example, in Indonesia, the decrease was 7.2 months (52%).

Efficiency was further evidenced by a reduction in queries; as shown in Table 2, the Philippines and Thailand received no additional questions from their respective NRAs during the national stage for PAC.

Regional Case Studies: Navigating Local Landscapes

Malaysia

As the Lead NRA, Malaysia’s reference to both TGA and EMA (i.e., dual-assessment reports) provided insights into the critical challenges associated with such an approach. During the national phase, the review incorporated queries from a secondary reference agency alongside the AJA framework. Moving forward, prioritizing a single primary reference agency assessment report would further reduce query burden and technical duplication.

Philippines

The Philippines Food and Drug Administration (PFDA) demonstrated the most significant efficiency gains. By utilizing the AJA pathway, the PFDA shortened the PAC approval timeline to 6.3 months, an acceleration from the 9-month standard. Most importantly, they fully accepted the joint assessment findings without issuing separate national queries, demonstrating true operational reliance.

Thailand

Thailand’s participation was built on a strong foundation; its national pathway for biologic PACs already aligns with European Medicines Agency (EMA) and WHO variation guidelines.

Indonesia

The sponsor’s experience with Indonesia highlighted the need for regulatory formalization. Because collaborative pathways are not yet integrated into Indonesia’s national guidelines, the NRA conducted a full local review in parallel with the joint assessment, which led to a different timeline between local versus AJA. The specific local timeline is 4.7 months for LE and 1.6 months for PAC.

Regulatory Convergence and Reliance

The pilot proved that the AJA framework can successfully drive regulatory convergence. Participating NRAs displayed increased alignment in scientific conclusions, leading to waiving of specific local requirements (e.g., post-change Certificates of Analysis) and reducing duplication by placing greater trust in the Assessment Report generated by the reference agency.

Furthermore, the “Strategic Advisory Support” model proved invaluable. The TGA’s mentorship, facilitated by the WHO, allowed the Lead NRA to demonstrate independent capability while benefiting from international peer-to-peer support, building the expertise necessary to sustain a long-term reliance-based ecosystem.

Recommendations for the Road Ahead

To transform the AJA pathway into a sustainable, lifecycle management procedure, five core actions are recommended:

• Formalize AJA in National Regulations: NRAs must integrate AJA as a recognized national pathway to eliminate “dual-track” evaluations and resource-heavy parallel reviews.
• Optimize Digital Workflows: Transition to a more efficient digital standard to reduce duplication of effort.
• Adopt a Unified Primary Reference Framework: NRAs should agree to prioritize a single primary reference authority to avoid the complexity of including queries from the secondary reference agency during the local approvals.
• Harmonize Variation Guidelines: Maintain continuous alignment with international standards (such as the EMA and WHO) to prevent change classification inconsistencies.
• Formalize Advisory Engagement Mechanisms: Establish structured pathways via the WHO for strategic advisors to ensure consistent mentorship during complex evaluations.

Ultimately, expanding the AJA framework from initial approval to lifecycle management is a vital step toward a harmonized regulatory environment, ensuring faster, more predictable access to life-saving medicines across ASEAN.

Acknowledgements

The authors extend their appreciation for the support and contributions provided to this pilot and the development of this article by Ehab Taqieddin, Srinivasan Kellathur Nadathur, Suat Gnoh Por, Ran Zhang, Fedina Devi Valentina, Jinwara Srisunacua, Robelle Benemerito, Joanna Waugh, Lauren Lord, Monica Habib, and Win Nie Lee.

n recent years, China’s healthcare reform has been largely focused on speed, particularly through the acceleration of regulatory review processes and the expansion of patient access to innovative medicines. Regulatory timelines have shortened through the introduction of flexible pathways such as priority review, breakthrough designation, and conditional approval, while clinical development has been further accelerated by the implementation of a 30-day review timeline for IND applications. As a result, China’s historical drug lag has narrowed, with an increasing number of products now submitted simultaneously or even first in China within the global landscape.

In 2025, the National Medical Products Administration (NMPA) approved a record number of new medicines. In parallel, the updating mechanism of the National Reimbursement Drug List (NRDL) has shifted from a multiyear cycle to an annual process, shortening the time between regulatory approval and reimbursement listing under the national health insurance system. This emphasis on speed has become a defining and widely recognized part of China’s healthcare reform.

However, another message emerged clearly from the China Town Hall at DIA Europe 2026: China’s next phase may be shaped not only by how quickly medicines reach the market, but by how they demonstrate value after launch through the National Healthcare Security Administration’s (NHSA’s) latest initiative: A Real-World Value Evaluation system to support health insurance decision-making, described as the “R-VALUE” framework, aimed at promoting the systematic generation of Real-World Evidence (RWE) to inform post-market evaluation of innovative health technologies.

A Still-Evolving Reform Story

China’s regulatory reforms have focused on faster approval and on encouraging simultaneous global development and submission of medicines; this agenda remains strong and evolving. But the R-VALUE framework announced in January 2026 (Draft guidance issued in Chinese only) made clear that the policy conversation is now moving further to payer decision-making. The question for China is no longer only how to bring new products to market more quickly, but also how to use health insurance resources in a way that is fair, sustainable, and more closely aligned with real patient benefit in China. In a nutshell, the NHSA R-VALUE framework aims to use trusted RWE to assess the clinical and broader value of medicines across their lifecycle to support reimbursement and other healthcare decisions. The public consultation on the framework concluded on 30 January 2026, and the pilot initiative is already operational. Under the implementation plan, 2026 is designated as the practice stage, followed by further phased development and application in 2027.

This shift is important because it changes the role of evidence in reimbursement decision-making. The payer is no longer asking only whether a medicine works under ideal or controlled trial conditions. Instead, it is asking how the medicine performs in real clinical practice, how much incremental benefit it provides compared with existing options, which patient populations benefit most, and whether that level of value is sufficient to justify public reimbursement. The NHSA’s R-VALUE framework is explicit on this point: The draft guidance published in January 2026 prioritizes evaluating medicines approved by NMPA on the basis of pivotal trials using single-arm designs or surrogate endpoints, especially conditionally approved medicines, and encourages the use of clinical endpoints such as overall survival.

More Than Just Another RWE Initiative

The use of RWE in regulatory and health technology assessment (HTA) decision-making is not new. Previous research has shown that regulatory and HTA agencies have increasingly incorporated RWE into their evaluations, with many authorities issuing official guidance on the generation and use of RWE. Since 2020, the Center for Drug Evaluation (CDE) of the NMPA has released a series of technical guidelines covering the generation, quality requirements, study design, and regulatory application of RWE across the product lifecycle. These guidelines clarify when and how RWE may be used to support drug approval, indication expansion, label modification, and post-marketing safety evaluation, with particular emphasis on data governance, bias control, and methodological rigor.

Building on this, the new direction in China is more than just another call for more real-world evidence; it’s a systematic framework from concept through methodology and to structural setup in order to use the RWE to directly support payer decision-making. The NHSA R-VALUE draft guidance outlines a structured architecture for the R-VALUE framework built around four core elements:

1. Common technical standards for study design, data sources, and analytical methods;
2. A standardized seven-step process spanning proposal development, protocol design, implementation, reporting, and data archiving;
3. A national network of 79 designated trusted sites within China to ensure data quality and scientific credibility; and
4. A clear focus on assessing the real-world clinical and economic value of innovative technologies in routine clinical practice.

This framework is supported by policy incentives. For example, two potential mechanisms were proposed in the draft guidance that linked to RWE in the National Reimbursement Drug List (NRDL) process. First, a newly approved drug with a completed value assessment with relevant RWE results may receive flexible pricing incentives during NRDL negotiations. Second, for drugs with insufficient evidence or uncertainty around efficacy/safety, a tiered incentive mechanism can be provided during the NRDL process on the condition that companies commit to conducting post-listing RWE studies. However, these incentives are accompanied by accountability measures: if the promised studies are not completed, or if the resulting evidence does not confirm the expected value, payment terms may be adjusted and the medicine may be subject to renegotiation.

Seen from this perspective, China is not just asking for more data, it is moving toward a systematic approach to incorporating RWE into reimbursement decision-making.

A Direction That Resonates Internationally

From an international perspective, these underlying questions in China are also being considered by many other health systems:

• How to assess value when clinical trial evidence is limited or based on surrogate endpoints;
• How to manage the uncertainty in accelerated approvals; and
• How to use RWE in decision-making without compromising methodological standards.

Randomized controlled trials (RCTs) remain essential in regulatory and reimbursement decision-making, but RWE can help determine a treatment’s benefits in routine clinical care, how patient adherence influences real-world value, whether comparative effectiveness can be better understood in the absence of direct head-to-head trials, and longer-term safety, outcomes, and economic impact.

Several processes and mechanisms are in place internationally: The European Medicines Agency’s (EMA) DARWIN EU initiative represents a federated real-world data network across Europe to generate RWE studies that inform regulatory decision-making. In England, NICE’s Managed Access (MA) allows patients to access promising new treatments for a defined period while further data collection such as RWE is conducted to address clinical or cost-effectiveness uncertainties.

In this sense, China is part of a broader global discussion, but it is doing so with increasing scale and ambition: China is not only a major commercial market; it is increasingly a market whose payer decisions may shape how global companies think about the evidence they generate across the product lifecycle.

Looking Ahead

Methodological and structural guidances make this ambition clear. However, how this framework will play out in practice remains unknown. Key questions include:

• How predictable will the system be for companies that must decide whether to invest in RWE generation?
• Which outcomes will matter in decision-making, such as survival, functional status, and quality of life, or treatment persistence and adherence?
• How transparent will public reporting of methods and results be?
• How will incentives for the generation and use of RWE be operationalized within the national reimbursement process?

An additional open question is how far evidence generated in China will travel usefully across borders, and to what extent it may inform payer or HTA discussions in other jurisdictions.

The answers to these questions will be important factors in determining whether the new framework evolves into a durable decision-making tool.

The NHSA draft guidance addressed some of these potential challenges by emphasizing unified guidance, verifiable data, robust quality control, and early and broad participation from key stakeholders. However, the ultimate measure of success will be whether these principles translate into evidence that can be used for payer decision-making, and whether patients ultimately gain better access to innovations.

For the international pharmaceutical industry and researchers, this is a moment worth watching closely. China is not merely adding another RWE initiative; it is building an emerging, structured, payer-oriented value evaluation system, one that remains in active development and will require further implementation experience before its predictability and impact can be fully assessed. China’s earlier reforms demonstrated what could be achieved when the system is focused on speed to innovation. Its next phase is to assess how a major health system determines which innovations are truly worth paying for, and how integrated evidence generation plans from RCT to RWE will support regulatory and payer decision-making.

ver the past decade, China’s pharmaceutical research and development (R&D) has been significantly transformed. Systemic regulatory reforms launched in 2015—including clinical trial licensing, rolling submissions, and expedited approval pathways—sharply accelerated development timelines and released a wave of domestic innovation.* China has emerged as a major source of global pharmaceutical innovation, accounting for nearly half of new drug molecules entering human trials in the first half of 2025. At the same time, domestic developers have achieved several world-first approvals in novel therapeutic modalities, reflecting China’s transition from a fast follower to an increasingly important innovation contributor.

Overall Comparison: Local Companies vs. MNCs

Local companies hold a clear early-stage lead: Their median 37.8 months from IND to the start of pivotal trials compares to 56.5 months for MNCs from 2023-2025; this gap has widened to 18.7 months from 9.3 months in 2020-2022. In phase 3, the two are essentially level at about 34 months each.

Performance of Leading Compounds

The top 10 fastest developed compounds (the 10 approved products with the shortest development cycles, as explained above) in China and global markets represent the peak development velocity for both groups (Figure 3 and Figure 4). Efficiency in the overall cycle has reached parity within this highest performance tier. In oncology, leading assets from MNCs achieve an overall development timeline of 51.2 months, while leading local companies further compress it to 36.8 months. Overall, oncology demonstrates higher development efficiency than non-oncology therapeutic areas. This suggests that in indications with high unmet medical needs, stronger regulatory support, and more focused endpoint design, speed advantages are more readily amplified and translated into competitive advantage.

Local companies maintain a pronounced velocity lead in early-phase oncology studies. The most accelerated local asset (finotonlimab) completed its early-phase development in just nine (9) months, outperforming the fastest MNC project by approximately 10 months, as the latter required 19.1 months to reach the same milestone. This gap reflects not only faster execution, but also efficiency in project decision-making, trial design, regulatory engagement, and resource coordination. In contrast, local companies show little acceleration advantage over MNCs in early-stage non-oncology development.

MNCs demonstrate superior speed and certainty from NDA submission to approval. This advantage is particularly pronounced in oncology, where the fastest MNC project achieved approval in just 2.6 months, compared with 6.3 months for the fastest local projects. Meanwhile, oncology products generally experience shorter approval timelines than non-oncology products.

Overall, local companies are raising expectations for early-stage execution, while MNCs continue to define standards in global development and regulatory excellence. Future leaders will be those that combine the best of both models—speed, scientific rigor, and global evidence generation—to deliver breakthrough therapies to patients faster.

Key Factors Driving the Performance Gap

Analysis of leading cases points to three drivers behind the local companies’ early-stage speed: aggressive early regulatory strategies, flexible execution, and a decisive shift to in-house clinical operations. Together they explain the early-phase agility—and the contrast with MNC operating models.

• Full use of policy advantages and calculated early clinical risk. For Class I innovative products with a globally validated Mechanism of Action (MoA), local companies fully exploit China’s regulatory pathways and adopt more aggressive early designs, including single-arm and seamless phase 1/2 studies. In oncology, these designs accelerated approvals well beyond the traditional parallel or placebo-controlled studies that MNCs favor for global data consistency.
• Accelerated execution through flexible local processes. Local companies bypass the protracted global review cycles typical of MNCs, using streamlined procedures for generating site contracts and Clinical Study Reports (CSRs). Some local models let early-phase Investigator-Sponsored Trials (ISTs) reach a “Go or No-Go” decision in as little as three days and finalize protocols within 1–2 months, whereas MNCs often need an added 2–4 weeks to satisfy global Standard Operating Procedure (SOP) requirements and internal approvals.
• Established in-house clinical operations and greater investment. Leading local companies have scaled internal teams that run a high share of their trials, gaining a 10%–30% speed increase over external Contract Research Organizations (CROs) through deeper product understanding and cross-functional coordination. MNCs are gradually building local teams too, but the aggressive resource scaling of local developers continues to drive their early-stage advantage.

These patterns reflect different strategic bets on speed versus regulatory rigor. For local industry, faster early phases are a market-entry advantage: by combining efficient decision-making with calculated risk-taking, they prioritize early regulatory engagement and positioning, laying the foundation to capture global first-in-class opportunities.

Crucially, this pursuit of speed must not compromise clinical rigor or data quality—and here the consistent performance of MNCs sets the industry benchmark. Their longer entry timelines largely reflect the complexity of Multi-Regional Clinical Trials (MRCTs) and alignment with diverse regulatory requirements across markets, including primary launch regions such as the US; in return, robust protocols and high-quality execution deliver greater certainty at final approval.

Outlook

The speed dynamics between local companies and MNCs show that development efficiency is now a core component of competitive advantage—and a vital lever for addressing unmet clinical needs.

As China establishes itself as a pioneering global R&D hub, both local and multinational companies can turn localized strengths—clinical flexibility and regulatory support—into synchronized global development. Integrating region-specific regulatory advantages can convert early-phase momentum into a sustainable competitive edge.

Ultimately, this alignment translates innovation into earlier market presence and greater product value, underscoring the decisive role of R&D and registration velocity on the global stage.

reventive medicines can spare people from serious illness, reduce pressure on health systems, and are often highly cost-effective in the long term. The problem is that our clinical and care systems are built for treating patients when they become sick rather than avoiding ill health in the first place.

Key points

• Prevention is a powerful tool in public health with potential to improve lives and support health service sustainability;
• Preventive health goes beyond lifestyle change to include immunization and medicines that reduce the risk of illness;
• Established systems are designed for therapeutic interventions and may be suboptimal for prevention strategies;
• New regulatory and access approaches are needed.

Beyond Lifestyle Changes

The fundamental concept of avoiding ill health rather than trying to fix problems when they arise is one most people can embrace. The old adage “An ounce of prevention is worth a pound of cure” is inherently appealing. As prevention is not only better for individuals, but often more efficient and cheaper for both individuals and society, it has become an imperative in the era of aging populations and rising demands on health services.

However, our view of prevention tends to be reduced to a set of lifestyle interventions. This puts the burden on people to manage their own behavioral risk factors: Eat well, exercise, quit smoking. While this remains sound advice, it reflects a mindset that separates prevention from medicine and the growing innovation in the field. This line of thinking sees preventive measures as a matter for individuals and limits our view of “medical interventions” to the treatments that are developed, regulated, and administered by the wider medical system.

Modern medical science, of course, is more complicated than that. It is also more interesting, more dynamic, and more exciting. Advances in our understanding of why things sometimes go wrong in the cells and systems that make up our bodies have, for decades, been changing how we think about health. While the power to predict illness is imperfect, we are better placed than ever before to identify markers of disease years—even decades—before symptoms emerge.

Several preventive medicinal products have overcome regulatory and access barriers to reduce episodes of ill health and save lives. Statins are widely used to prevent heart attacks and strokes by reducing cholesterol, a major risk factor for cardiovascular disease. Vaccines against human papillomavirus (HPV) are driving down infections that cause precancerous lesions, ultimately preventing cervical cancer. The potential of GLP-1 agonists to prevent obesity-related illness is an area of enormous interest to researchers, payers, and patients alike.

These products illustrate the need to think about surrogate endpoints given, for example, the time lag between a HPV vaccine administered in adolescence and the nonoccurrence of cancer decades later. They also show the power of prevention in protecting population health. However, there is scope to achieve much more by reimagining incentives and pathways for preventive interventions.

Shifting Minds and New Incentives

Notwithstanding these hurdles, science is moving forward. This demands a collective effort to address psychological, cultural, and practical barriers in order to help build a prevention-focused health ecosystem. Not only should all stakeholders engage with the public and policymakers to support a more long-term view of protecting health, but we must also work together to ensure that research and development, regulatory, manufacturing, and access pathways and incentives are aligned with prevention.

Europe’s regulatory system has experience in adapting to meet an agreed goal. For example, the Orphan Medicines Regulation has had a transformative impact on the field of rare diseases. The Paediatric Regulation has increased research on children’s healthcare. Support for new antibiotics to help combat antimicrobial resistance (AMR), and ongoing stakeholder dialogue on innovative incentive models, show a capacity for fresh thinking to advance shared policy goals.

Europe also has a strong record of deploying public-private partnerships to clear bottlenecks in the system. The Innovative Medicines Initiative and its successor, the Innovative Health Initiative, have supported projects designed to develop digital endpoints, novel biomarkers, and data governance. These projects facilitate early engagement between academia, developers, and regulators that helps to shape regulatory science and, ultimately, promises to bring new solutions closer to patients.

n April 2026, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) became the first regulatory authority in the world to mandate eCTD v4.0 for all new drug submissions. For someone like me who has followed eCTD developments closely since the early days of v4.0 adoption, this milestone is significant. Five months after PMDA began accepting v4.0 submissions on a voluntary basis in April 2022, my team completed what we believe was Japan’s first formal v4.0 submission. This experience highlighted a gap between a feature being available and a feature being genuinely useful in practice.

The Keyword Incentive Problem

Among eCTD v4.0’s most promising capabilities is its structured keyword system. Compared to v3.2.2, keywords enable richer document metadata, supporting faster review, improved cross-document referencing, and the kind of machine-readable structure that could one day underpin AI-assisted regulatory review.

In practice, however, keyword adoption has been inconsistent. Within one organization where I worked, the policy at the time was unambiguous: all optional keywords would be omitted. The reasoning was equally straightforward: there was no direct, tangible benefit to the applicant for including them.

This is not an isolated case. It reflects a structural dynamic that applies across most industries: When a feature is optional, it will be adopted in proportion to the perceived value it creates for the party bearing the cost of implementation. Where that value is unclear or accrues only to the regulator, adoption by industry will remain low.

In this case, three levers currently exist for changing this dynamic:

1. Agencies Demonstrating the Value
   PMDA has taken steps that other agencies would do well to emulate. The agency has publicly disclosed how it uses keywords internally during review (for example, grouping nodes by keyword can make the data easier to read) and has shown how those keywords surface in PMDA’s own eCTD viewer. This transparency signals to industry that the metadata they provide is actually being used—and used in specific, meaningful ways. It would be a welcome development if other authorities adopted a similar approach.
2. Vendors Reducing the Cost
   Submission management systems can play a significant role in shifting the cost-benefit calculation. For example, the departments responsible for compiling the eCTD and preparing its documents are often separate in Japan. The former has a deep understanding of the keywords themselves within the eCTD, while the latter can better determine which keywords should be assigned and verify whether the assigned keywords are correct. Designing a system that avoids this cross-departmental workflow and allows for cross-referencing documents, the eCTD framework, and a pre-organized keyword list to automatically and appropriately assign keywords might help alleviate the reluctance of field staff to assign keywords. When keyword assignment is automated, context-aware, and validated in real time, this barrier to compliance comes down. As vendors build smarter tooling, the threshold at which optional features become worth using changes.
3. Applicants Discovering Their Own Value
   The most powerful lever—and the most underexplored—is the one applicants hold themselves. Keywords are document metadata, and metadata have uses beyond regulatory submission. For instance, the same structured keyword data that support PMDA review could feed internal AI-assisted document classification, retrieval, or quality systems. Organizations that begin to see their submission data as a strategic asset will find incentives that external mandates cannot create.

Document Reuse: Useful in Theory, Costly in Practice

A second signature capability of v4.0 is document reuse: the ability to reference a previously submitted document rather than resubmit it in full. On paper, this reduces redundancy.

In practice, this experience was somewhat disappointing. Document reuse requires confirming, each time, what was submitted, where, and under which submission context. The operational overhead of tracking reuse eligibility outweighed the savings of not resubmitting.

The conclusion was pragmatic: resubmitting a previously submitted document every time was actually simpler.

This is not a failure of v4.0’s design. In Japan, eCTD submissions are divided into fine-grained Applications, making the submissions themselves simple enough that document reuse rarely delivers its full value in Japan. Unless the time-consuming effort of reuse is dramatically reduced, it will be difficult to justify adopting this feature. For example, if you do not plan to reuse the document, you can include the CTD document number in the document title. This makes it easier to create external links. If you want to create a link to the PDF for Section 5.3, you simply need to look at the far left of the title. Conversely, if you plan to reuse the document, you should not include the CTD document number in the title. This is because the same CTD number may not be assigned for the next submission. While the cost of paying attention to details like this is not significant, our team concluded that it outweighs the benefits gained.

In contrast, the EU—where documents are commonly shared across multiple regulatory authorities—stands to benefit more from avoiding resubmission. Similarly, in the US, where a single Application can be large in scope and may involve the same documents multiple times, resubmitting each time may not be the intuitive choice.

A Small but Telling Success

It would be unfair to catalog only these gaps. One episode from the transition period illustrates where v4.0’s architecture genuinely delivers.

In March 2025, PMDA added a Status column to all controlled vocabularies. The change looks trivial, but had it been attempted under v3.2.2, it would have required revising the eCTD schema itself through the ICH consensus process. For vendors of viewers and submission tools, this kind of update would have also meant substantial remediation work with the potential to ripple across entire systems.

Under v4.0, controlled vocabularies are designed from the start as an independently updatable variable region of the standard. Adding the Status column is a more significant change than simply adding a row. Even so, this change remained within the vocabulary layer, and PMDA was able to add the Status column without altering the standard itself. And because vendors build their products on the same premise, they accommodate such changes smoothly. The modular separation between the document specification and the regulatory vocabulary layer is not an abstract design principle; it is a practical capability that is already being exercised.

Deeper Value: Flexibility for an Evolving Landscape

The pharmaceutical modality landscape is expanding faster than any single regulatory framework can track in real time. Low-molecular-weight compounds, monoclonal antibodies, nucleic acid therapeutics, combination products, and modalities that do not yet have established categories are all moving through development pipelines simultaneously.

Under v3.2.2, incorporating a genuinely novel document type or classification requirement could require revising the standard itself—a slow, resource-intensive process with global coordination implications. Under v4.0, the controlled vocabulary and keyword layers can absorb much of that change without touching the core architecture.

This flexibility is v4.0’s most significant long-term contribution. It is also, for now, its most underappreciated one. Industry has not yet encountered enough of the scenarios that v4.0 was built to handle gracefully.

A Practical Note on Code Management

For organizations navigating the operational realities of v4.0 implementation, codelist management deserves specific attention. For internally managed submissions, modern submission systems handle most of the complexity. Where contract research organizations or external partners are involved, the challenge shifts to ensuring that codelist versions are synchronized across organizations, requiring either shared systems or explicit codelist governance protocols.

While not exclusive to v4.0, codelist management matters more than it did with v3.2.2.

From Compliance to Capability

Japan’s mandatory transition to eCTD v4.0 poses a question that mandates alone cannot answer: Now that the format is required, who will design the incentives that make its capabilities worth using?

The answer is not straightforward, because the work belongs to all three constituencies simultaneously:

• Regulators must demonstrate how structured metadata is used in review, making the value of compliance visible to applicants.
• Vendors must reduce the friction of implementation, shifting the cost-benefit equation.
• Applicants must look beyond the submission itself, identifying how v4.0’s richer data architecture creates value within their own organizations.

If v4.0 ends its first mandatory chapter as nothing more than an updated file format for existing workflows, the standard will have fallen short of its purpose.

The transition from mandatory compliance to genuine capability is the next frontier. It will require deliberate effort from regulators, vendors, and industry alike.

he Singapore Association of Pharmaceutical Industries (SAPI), which recently celebrated its 60th anniversary, represents research-based biopharmaceutical companies in Singapore and serves as a platform for constructive engagement among industry, regulators, and other healthcare stakeholders. A key partner in this ecosystem is Singapore’s Health Sciences Authority (HSA), which marked its 25th anniversary in 2026.

A Modern, Risk-Based Regulatory System

From the Singapore-based industry perspective, the past decade (2016-2026) has been particularly significant, marked by regulatory innovation, international collaboration, and close regulator-industry engagement that have supported timely access to innovative health products.

While Singapore is a relatively small domestic market, it serves as a leading regional hub for pharmaceuticals, biotechnology, and medical technology. More than 60 biopharmaceutical manufacturing facilities operate in Singapore, producing a broad range of products, including active pharmaceutical ingredients, biologics, cell therapies, and antibody-drug conjugates. With biopharmaceutical industry output exceeding S$18 billion in 2023, Singapore has developed a strong ecosystem that supports close regulator-industry collaboration and regulatory innovation. Consistent with this environment, Singapore’s regulatory environment for health products has evolved from a product-specific framework into a more integrated, risk-based, lifecycle-oriented system. This evolution has strengthened regulatory predictability and enabled more efficient oversight across the product lifecycle.

The establishment of the Health Products (Therapeutic Products) Regulations 2016, which brought the regulation of pharmaceutical products under the Health Products Act, marked one key milestone. Consolidating registration, licensing, and supply-chain controls within a single legislative framework created a more integrated regulatory model and provided greater clarity across the product lifecycle.

As HSA’s regulatory approach has matured, assessment and oversight of pharmaceutical products have become progressively more risk-proportionate with continuous refinement of registration requirements to streamline processes, improve predictability, and clarify documentation expectations. One notable example was the expansion in 2022 of post-approval changes permitted under the MIV-2 “Do-and-Tell” notification pathway, following optimization of the variation checklist. This reform demonstrates HSA’s continued efforts to calibrate regulatory oversight according to product risk, reduce unnecessary regulatory burden, and support more efficient lifecycle management.

HSA has also developed fit-for-purpose regulatory frameworks and guidance for emerging technologies, including cell, tissue, and gene therapies, software as a medical device, digital health products, AI-related tools, and laboratory-developed tests (Table 1). These initiatives demonstrate HSA’s commitment to ensuring that regulatory requirements continue to evolve alongside scientific and technological advances.

Table 1: Key Regulatory Initiatives, 2016–2026.

Singapore’s Stronger Global Regulatory Partnerships

HSA’s international collaboration is an important enabler of Singapore’s pharmaceutical ecosystem and can support more timely access to innovative health products. HSA has achieved World Health Organization (WHO) maturity level 4 (ML4) status and has subsequently been designated a WHO-Listed Authority (WLA) for Medicines in 2022 and 2023 respectively. (FDA, EMA, TGA, and PMDA became WLA later than HSA, and they went through an abbreviated assessment.) More recently, HSA was the first regulator to achieve the highest WHO maturity level 4 through a comprehensive assessment by WHO in 2026. The WHO benchmarking framework evaluates regulatory authorities against over 260 indicators and is on a voluntary basis. This demonstrates HSA’s willingness to be benchmarked against global standards. (See Figure 1.) HSA is recognized as a reference authority by a growing number of regulators. For Medicines, this includes Australia, Brunei, Egypt, Hong Kong, Philippines, South Africa, Switzerland, the United Kingdom, and Uzbekistan. This facilitates expedited registration pathways for products that have received HSA’s approval.

Figure 1: HSA’s international recognition as a robust regulatory agency

At the regional level, HSA participates in the ASEAN Joint Assessment Procedure for Pharmaceutical Products, through which member states conduct simultaneous, coordinated assessments of the same marketing authorization application. For companies seeking registration across multiple ASEAN markets, this can reduce duplication of effort and support more consistent outcomes across the region.

In addition to multilateral platforms and regional mechanisms, HSA has also built strong bilateral partnerships and has more than 20 active memoranda of understanding (MoUs) with regulatory authorities globally (see Table 2 below). These formalize regulatory agencies’ commitments for partnerships and broaden opportunities for information sharing, capability building, joint initiatives, and regulatory innovation.

The UK-Singapore Regulatory Innovation Corridor is particularly significant for industry in terms of facilitating access to innovative products between these two markets. While still in pilot phase, its promise for coordinated early engagement with both HSA and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) can help developers anticipate requirements, improve development plans, and avoid unnecessary delay for breakthrough technologies.

Table 2: Bilateral agreements signed by HSA in 2026

For industry, this growing network has significant practical implications. Singapore’s integration into global and regional regulatory frameworks means that HSA assessments are increasingly recognized and leveraged by other authorities. This engagement can support more efficient inspections, clearer regulatory pathways, and earlier scientific dialogue, reduce duplication, and support more efficient multimarket registration strategies for applicants. Companies engaging with HSA can do so with confidence that its standards are internationally benchmarked and that its relationships with peer regulators continue to grow.

The Value of Regulator–Industry Partnership

Over the years, HSA and SAPI have established a strong partnership founded on a shared commitment to public health, timely patient access to innovative medicines and vaccines, and regulatory excellence. A key strength of this partnership is the regular engagements between the SAPI Regulatory Affairs Committee (RAC) and HSA, which provide a platform for dialogues on regulatory developments, implementation challenges, and opportunities for continuous improvement. More recently, SAPI RAC collaborated with HSA in the Health Products Regulatory Conference BioPharma Day 2025, bringing together regulators, policymakers, and industry representatives to exchange perspectives on regulatory science, artificial intelligence in regulatory affairs, advanced therapies, and submission excellence.

Within SAPI RAC, several working groups facilitate structured engagement on emerging regulatory topics with HSA. Through consultations on policies, guidelines, and implementation experiences, these groups provide industry feedback to support practical regulatory solutions. A notable example is the close collaboration between SAPI RAC and HSA in reviewing and optimizing the variation guidelines and checklists to ensure they remain aligned with evolving international regulatory practices. The working groups have also contributed to discussions on digitalization initiatives such as e-labeling and eCTD implementation, as well as emerging regulatory frameworks for innovative treatments such as cell and gene therapies.

SAPI contributes to international regulatory collaboration beyond Singapore through its participation in the network of pharmaceutical industry trade associations across the five Access Consortium member countries. Together with its international counterparts, SAPI engages Access Consortium regulators and provides industry recommendations through position papers to strengthen collaborative review pathways, particularly the New Active Substance Work-Sharing Initiative (NASWSI). These efforts support greater transparency, predictability, and regulatory convergence, and contribute to the continued development of the Access pathway to facilitate more timely access to innovative medicines. Within ASEAN, SAPI is actively involved in ASEAN pharmaceutical harmonization at the Implementation Working Group under the ASEAN Pharmaceutical Product Working Group where SAPI is currently the chair of the ASEAN Pharmaceutical Research Industry Association.

The value of such international collaboration was further demonstrated through SAPI’s engagement with HSA and the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) during the ICH Assembly held in Singapore in November 2025. The engagement brought together HSA, industry leaders, and IFPMA representatives to exchange perspectives on ICH guideline development, HSA’s ICH implementation journey, and opportunities for collaboration. One example is the revised ICH E6(R3) Good Clinical Practice guideline: ahead of its implementation in Singapore on 1 January 2026, SAPI members took part in HSA-led training, workshops, and stakeholder engagement sessions. These initiatives strengthened regulator-industry alignment and supported the effective adoption of internationally harmonized standards.

Looking Ahead: Building on a Strong Foundation

HSA has played a pivotal role in shaping a modern, robust, predictable regulatory environment in Singapore. For industry, one of the most significant developments has been the growing availability of international collaborative pathways such as the Access Consortium and Project Orbis, which enable companies to pursue earlier, more coordinated medicine launches across multiple countries.

As regulatory pathways have evolved, proactive planning and agile regulatory strategies have become increasingly important for improving efficiency, optimizing submission sequencing, and maintaining compliance throughout the product lifecycle.

Looking ahead, there are opportunities to build on HSA’s WHO maturity level 4 and WHO-Listed Authority status to strengthen international partnerships and translate collaboration agreements into transparent, scalable, measurable facilitated pathways. Industry sees particular value in establishing clear eligibility criteria, aligned submission windows, predictable timelines, mechanisms for confidential information exchange, consistent post-approval requirements, and regular regulator-industry dialogue. Industry can, in turn, support implementation by sharing operational experience, identifying practical challenges, providing technical expertise, and encouraging use of collaborative pathways where appropriate. These efforts can strengthen regulatory capacity, build trust among authorities, reduce unnecessary administrative burden, and reinforce Singapore’s position as a launch and innovation hub. Continued regulator–industry engagement will be important to realize these benefits while maintaining high regulatory standards and supporting timely access to safe, effective, innovative health products.

Singapore’s experience demonstrates how sustained collaboration between regulators and industry can strengthen public health, support innovation, and improve access to safe and effective medicines. Building on the strong foundations established over the past 25 years, continued partnership between HSA and industry will be central to shaping the next chapter of Singapore’s regulatory development.